Molecular and Cellular Physiology and Biophysics of the Heart

Heart disease is the biggest killer in the society today. The function of the heart is governed by the cell biology and molecular physiology of the heart muscle. As such, the heartbeat, the rhythm, the force of the contraction, and irregularities thereof are controlled by the network of cells that make up the heart. In my laboratory, we study the heart muscle and its constituent cells under normal conditions, during pathologic conditions such as myocardial infarction, heart failure, and cardiac myopathies, as well as after exercise training in both health and disease. We do this to understand the heart better, and therefore be able to generate better therapies for the heart when something goes wrong and ultimately to reduce the impact of heart disease to the patient as well as the society as a whole. This includes studying the cellular and molecular events that underlie and translate into first a reduced and secondly an improved function. In order to do this, we employ a range of experimental models that mimic normal function, dysfunction, disease and exercise, as well as physiological, biophysical, electrophysiological, biochemical, and molecular laboratory methods.

Heart disease is the leading cause of disability and death in the western world including the UK, with a limited scope for treatment. The 5-year mortality of heart failure; a severe form of heart disease is 50-70%, of which ~50% die of progressive pump failure chiefly caused by abnormal contractile function and ~50% of sudden arrhythmic events. Both abnormal contractile function and many arrhythmic events are further mechanistically explained by abnormalities in cardiomyocyte excitation-contraction coupling. Excitation-contraction coupling is initiated by the sarcolemmal and transverse tubule depolarisation that activates the voltage-sensitive L-type Ca2+ channels; this inward Ca2+ current causes further Ca2+ release from the sarcoplasmic reticulum via the Ca2+ channel ryanodine receptor-2, and the resultant increase of the intracellular Ca2+ concentration evokes myofilaments contraction (systole). The activities of the sarcoplasmic reticulum Ca2+ ATPase SERCA2a and the sarcolemmal Na+/Ca2+-exchanger restore the cytoplasmic Ca2+ to resting levels (diastole). All of the proteins involved may be modulated by different small molecules that interact with the excitation-contraction coupling process. Cardiac contraction is directly governed by this process, but certain ventricular arrhythmias are also initiated by aberrant sarcolemmal and intracellular control of the ions involved in excitation-contraction coupling such as Ca2+, Na+, and K+.

For this reason, understanding, modulating, and therapeutically intervening with the excitation-contraction coupling process or the small molecules that interact with it becomes important, in order to reduce the burden of heart disease and failure. This therefore has consequences for the individual heart disease patients and the society alike, especially as the management of heart disease is costly and strains economies from households to national GDPs. Thus, the socioeconomic consequences of the heart failure pandemic are enormous and need be dealt with by more affordable solutions.

Importantly, exercise training provides an inexpensive and underdeveloped benefit to the patient because it physiologically improves the function of the heart directly through its modulation of excitation-contraction coupling and indirectly through its modulation of small molecules that subsequently interact with excitation-contraction coupling. Therefore, exercise training improves the function and control of the heart, which has been evidenced to support both athletes seeking to improve sporting performance, regular healthy individuals seeking to improve work capacity for daily functioning, and patients with heart and other cardiovascular diseases, hypertension, diabetes, metabolic syndrome and disease, muscle disorder, and several other dysfunctions.

Therefore, a detailed examination of cardiac function and cardiomyocyte biology in normal, dysfunctional, and failing hearts in the absence and presence of exercise training is necessary to understand how cardiac health may be modulated to benefit individuals, patients and the society, by exercise training as an affordable complementary option to other established treatments. Secondly, this research also has the power to reveal molecular aims for improving cardiac health that may be targeted by new experimental interventions.


  1. Kemi OJ, Haram PM, Hoydal MA, Wisloff U, Ellingsen O. Exercise training and losartan improve endothelial function in heart failure rats by different mechanisms. Scand Cardiovasc J 2013 Jan 3 [Epub ahead of print]
  2. Kaurstad G, Alves MN, Kemi OJ, Rolim N, Hoydal MA, Wisloff H, Stolen TO, Wisloff U. Chronic CaMKII inhibition blunts the cardiac contractile response to exercise training. Eur J Appl Physiol 2012;112:579-588.
  3. Kemi OJ, MacQuaide N, Hoydal MA, Ellingsen O, Smith GL, Wisloff U. Exercise training corrects control of spontaneous calcium waves in hearts from myocardial infarction heart failure rats. J Cell Physiol 2012;227:20-26.
  4. Kemi OJ, Ellingsen O. Cardiac hypertrophy, physiological. In: Mooren FC (Ed). Encyclopedia of Exercise Medicine in Health and Disease. Springer, Berlin, Germany 2012;171-175. ISBN 978-3-540-36065-0.
  5. Rognmo O, Kemi OJ, Wisloff U. Interval training. In: Mooren FC (Ed). Encyclopedia of Exercise Medicine in Health and Disease. Springer, Berlin, Germany 2012;470-473. ISBN 978-3-540-36065-0.
  6. Koch LG*, Kemi OJ*, Qi N, Leng SX, Bijma P, Gilligan LJ, Wilkinson JE, Wisloff H, Hoydal MA, Rolim N, Abadir PM, van Grevenhof EM, Smith GL, Burant CF, Ellingsen O, Britton SL, Wisloff U. Intrinsic aerobic capacity sets a divide for aging and longevity. Circ Res 2011;109:1162-1172. *Joint 1st author.
  7. Helgerud J, Rodas G, Kemi OJ, Hoff J. Strength and endurance in elite football players. Int J Sports Med 2011;32:677-682.
  8. Kemi OJ, Hoydal MA, MacQuaide N, Haram PM, Koch LG, Britton SL, Ellingsen O, Smith GL, Wisloff U. The effect of exercise training on transverse tubules in normal, remodelled and reverse remodelled hearts. J Cell Physiol 2011;226:2235-2243.
  9. Kemi OJ, Rognmo O, Amundsen BH, Slordahl SA, Richardson RS, Helgerud J, Hoff J. One-arm maximal strength training improves work economy and endurance capacity, but not skeletal muscle blood flow. J Sports Sci 2011;29:161-170.
  10. Smith GL, Reynolds M, Burton F, Kemi OJ. Confocal and multiphoton imaging of intracellular Ca2+. Methods Cell Biol 2010;99:225-261.
  11. Wang Y, Wisloff U, Kemi OJ. Animal models in the study of exercise-induced cardiac hypertrophy. Physiol Res 2010;59:633-644.
  12. Menzies P, Menzies C, McIntyre L, Paterson P, Wilson J, Kemi OJ. Blood lactate clearance during active recovery after an intense running bout depends on the intensity of the active recovery. J Sports Sci 2010;28:975-982.
  13. Kemi OJ, Wisloff U. Mechanisms of exercise-induced improvements in the contractile apparatus of the mammalian myocardium. Acta Physiol 2010;199:425-439.
  14. Kemi OJ, Wisloff U. High-intensity aerobic exercise training improves the heart in health and disease. J Cardiopulm Rehabil Prev 2010;30:2-11.
  15. Beisvag V, Kemi OJ, Arbo I, Loennechen JP, Wisloff U, Langaas M, Sandvik AK, Ellingsen O. Pathological and physiological hypertrophies are regulated by distinct gene programs. Eur J Cardiovasc Prev Rehabil 2009;16:690-697.
  16. Stolen TO, Hoydal MA, Kemi OJ, Catalucci D, Ceci M, Aasum E, Larsen T, Rolim N, Condorelli G, Smith GL, Wisloff U. Interval training normalizes cardiomyocyte function, diastolic Ca2+ control, and SR Ca2+ release synchronicity in a mouse model of diabetic cardiomyopathy. Circ Res 2009;105:527-536.
  17. Wisloff U, Ellingsen O, Kemi OJ. High-intensity interval training to maximize cardiac benefits of exercise training? Exerc Sports Sci Rev 2009;37:139-146.
  18. Haram PM*, Kemi OJ*, Lee SJ, Bendheim MO, Al-Share QY, Waldum HL, Gillian LJ, Koch LG, Britton SL, Najjar SM, Wisloff U. Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity. Cardiovasc Res 2009;81:723-732. *Joint 1st Author.
  19. Kemi OJ. Experimental evidence may inform the debate. J Appl Physiol 2009;106:345.
  20. Bye A, Hoydal MA, Catalucci D, Langaas M, Kemi OJ, Beisvag V, Koch LG, Britton SL, Ellingsen O, Wisloff U. Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO2max. Physiol Genomics 2008;35:213-221.
  21. Schjerve IE, Tyldum GA, Tjonna AE, Stolen T, Loennechen JP, Hansen HE, Haram PM, Heinrich G, Bye A, Najjar SM, Smith GL, Slordahl SA, Kemi OJ, Wisloff U. Both aerobic endurance and strength training programmes improve cardiovascular health in obese adults. Clin Sci 2008;115:283-293.
  22. Kemi OJ, Rognmo O, Wisloff U, Haram PM. Exercise training does / does not induce vascular adaptations beyond the active muscle beds. J Appl Physiol 2008;105:1008-1009.
  23. Tjonna AE, Lee SJ, Rognmo O, Stolen TO, Bye A, Haram PM, Loennechen JP, Al-Share QY, Skogvoll E, Slordahl SA, Kemi OJ, Najjar SM, Wisloff U. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome – a pilot study. Circulation 2008;118:346-354.
  24. Adamson M, MacQuaide N, Helgerud J, Hoff J, Kemi OJ. Unilateral arm strength training improves contralateral peak force and rate of force development. Eur J Appl Physiol 2008;103:553-559.
  25. Kemi OJ, Ceci M, Condorelli G, Smith GL, Wisloff U. Myocardial sarcoplasmic reticulum Ca2+ ATPase function is increased by aerobic interval training. Eur J Cardiovasc Prev Rehabil 2008;15:145-148.
  26. Bye A, Langaas M, Hoydal MA, Kemi OJ, Heinrich G, Koch LG, Britton SL, Najjar SM, Ellingsen O, Wisloff U. Aerobic capacity-dependent differences in cardiac gene expression. Physiol Genomics 2008;33:100-109.
  27. Kemi OJ, Ceci M, Wisloff U, Grimaldi S, Gallo P, Smith GL, Condorelli G, Ellingsen O. Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy. J Cell Physiol 2008;214:316-321.
  28. Kemi OJ, Ellingsen O, Smith GL, Wisloff U. Exercise-induced changes in calcium handling in left ventricular cardiomyocytes. Front Biosci 2008;13:356-368.
  29. Haram PM, Kemi OJ, Wisloff U. Adaptation of endothelium to exercise training: Insights from experimental studies. Front Biosci 2008;13:336-346.
  30. Ghouri IA, Kemi OJ, Smith GL. Temperature preconditioning: a cold-hearted answer to ischaemic/reperfusion injury. J Physiol 2007;585:649-650.
  31. Hoydal MA, Wisloff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil 2007;14:753-760.
  32. Kemi OJ, Hoydal MA, Haram PM, Garnier A, Fortin D, Ventura-Clapier R, Ellingsen O. Exercise training restores aerobic capacity and energy transfer systems in heart failure treated with losartan. Cardiovasc Res 2007;76:91-99.
  33. Kemi OJ, Ellingsen O, Ceci M, Grimaldi S, Smith GL, Condorelli G, Wisloff U. Aerobic interval training enhances cardiomyocyte contractility and Ca2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban. J Mol Cell Cardiol 2007;43:354-361.
  34. Hoydal MA, Wisloff U, Kemi OJ, Britton SL, Koch LG, Smith GL, Ellingsen O. Nitric oxide synthase type-1 modulates cardiomyocyte contractility and calcium handling: association with low intrinsic aerobic capacity. Eur J Cardiovasc Prev Rehabil 2007;14:319-325.
  35. Wisloff U, Haram PM, Kemi OJ. Genetic vs. acquired fitness: cardiomyocyte adaptations. In: Stocchi V, De Feo P, Hood DA (Eds). Role of Physical Exercise in Preventing Disease and Improving the Quality of Life. Springer, Milan, Italy 2007;61-81. ISBN 978-88-470-0375-0.
  36. Kemi OJ, Arbo I, Hoydal MA, Loennechen JP, Wisloff U, Smith GL, Ellingsen O. Reduced pH and contractility in failing rat cardiomyocytes. Acta Physiol 2006;188:185-193.
  37. Haram PM, Adams V, Kemi OJ, Brubakk AO, Hambrecht R, Ellingsen O, Wisloff U. Time-course of endothelial adaptation following acute and regular exercise. Eur J Cardiovasc Prev Rehabil 2006;13:585-591.
  38. Kemi OJ, Ellingsen O. Trans-sodium crocetinate does not affect oxygen uptake in rats during treadmill running. Scand J Clin Lab Invest 2005;65:577-583.
  39. Hoff J, Kemi OJ, Helgerud J. Strength and endurance differences between elite and junior elite ice hockey players: the importance of allometric scaling. Int J Sports Med 2005;26:537-541.
  40. Slordahl SA, Wang E, Hoff J, Kemi OJ, Amundsen BH, Helgerud J. Effective training for patients with intermittent claudication. Scand Cardiovasc J 2005:39:244-249.
  41. Kemi OJ, Haram PM, Loennechen JP, Osnes JB, Skomedal T, Wisloff U, Ellingsen O. Moderate vs. high exercise intensity: differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function. Cardiovasc Res 2005;67:161-172.
  42. Kemi OJ, Haram PM, Wisloff U, Ellingsen O. Aerobic fitness is associated with cardiomyocyte contractile capacity and endothelial function in exercise training and detraining. Circulation 2004;109:2897-2904.
  43. Kemi OJ, Hoff J, Engen LC, Helgerud J, Wisloff U. Soccer specific testing of maximal oxygen uptake. J Sports Med Phys Fitness 2003;43:139-144.
  44. Kemi OJ, Loennechen JP, Wisloff U, Ellingsen O. Intensity-controlled treadmill running in mice: Cardiac and skeletal muscle hypertrophy. J Appl Physiol 2002;93:1301-1309.
  45. Hoff J, Wisloff U, Engen LC, Kemi OJ, Helgerud J. Soccer specific aerobic endurance training. Br J Sports Med 2002;36:218-221.
  46. Wisloff U, Helgerud J, Kemi OJ, Ellingsen O. Intensity-controlled treadmill running in rats: VO2max and cardiac hypertrophy. Am J Physiol Heart Circ Physiol 2001;280:H1301-H1310.